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Thermodynamic profiling of inhibitors of Nrf2:Keap1 interactions.
- Source :
-
Bioorganic & Medicinal Chemistry Letters . Jan2016, Vol. 26 Issue 2, p526-529. 4p. - Publication Year :
- 2016
-
Abstract
- Keap1 binds to the transcription factor Nrf2 and negatively modulates the expression of genes involved in cellular protection against oxidative stress. Small molecules have been discovered to inhibit the Nrf2:Keap1 interactions and act as antagonists of Keap1. The affinities of these small molecules are not very high and need further improvement in follow up hit-to-lead programs. In addition to the affinity parameters K i , K d , and IC 50 thermodynamic parameters provide useful information for the selection and optimization of these hit molecules at the early stage of the lead discovery process. In this letter a tracer displacement assay was used to determine the thermodynamic signature of some of the known inhibitors of the Nrf2:Keap1 interaction. An optimized assay protocol is presented, which can be applied to other small molecules in hit-to-lead programs in a medium throughput manner. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0960894X
- Volume :
- 26
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Publication Type :
- Academic Journal
- Accession number :
- 112055791
- Full Text :
- https://doi.org/10.1016/j.bmcl.2015.11.082